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针对叶酸受体α的卵巢癌治疗策略。

Therapeutic strategies targeting folate receptor α for ovarian cancer.

机构信息

Department of Laboratory Medicine, Obstetrics & Gynecology and Pediatrics, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Center of Growth, Metabolism and Aging, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, Sichuan, China.

Department of Obstetrics and Gynecology, Chengdu Second People's Hospital, Chengdu, Sichuan, China.

出版信息

Front Immunol. 2023 Aug 30;14:1254532. doi: 10.3389/fimmu.2023.1254532. eCollection 2023.

Abstract

Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer, and presents a major clinical challenge due to limited treatment options. Folate receptor alpha (FRα), encoded by the FOLR1 gene, is an attractive therapeutically target due to its prevalent and high expression in EOC cells. Recent basic and translational studies have explored several modalities, such as antibody-drug conjugate (ADC), monoclonal antibodies, small molecules, and folate-drug conjugate, to exploit FRα for EOC treatment. In this review, we summarize the function of FRα, and clinical efficacies of various FRα-based therapeutics. We highlight mirvetuximab soravtansine (MIRV), or Elahere (ImmunoGen), the first FRα-targeting ADC approved by the FDA to treat platinum-resistant ovarian cancer. We discuss potential mechanisms and management of ocular adverse events associated with MIRV administration.

摘要

上皮性卵巢癌(EOC)是致死率最高的妇科癌症,由于治疗选择有限,因此带来了重大的临床挑战。叶酸受体α(FRα)由 FOLR1 基因编码,由于其在 EOC 细胞中的普遍高表达,成为了一种有吸引力的治疗靶点。最近的基础和转化研究探索了多种方法,如抗体药物偶联物(ADC)、单克隆抗体、小分子和叶酸药物偶联物,以利用 FRα 治疗 EOC。在这篇综述中,我们总结了 FRα 的功能以及基于 FRα 的各种治疗方法的临床疗效。我们重点介绍了 mirvetuximab soravtansine(MIRV),或 Elahere(ImmunoGen),这是 FDA 批准的首个用于治疗铂耐药卵巢癌的 FRα 靶向 ADC。我们讨论了与 MIRV 给药相关的眼部不良事件的潜在机制和管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9d/10499382/7e5f5bbfd912/fimmu-14-1254532-g001.jpg

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